                         SEQUENCE LISTING

<110>  ALDERBIO HOLDINGS LLC
       Mitchell, Danielle M
       Garcia-Martinez, Leon F
       Ojala, Ethan W
       Inan, Mehmet
       McNeill, Patricia D
       Latham, John
 
<120>  MULTI-COPY STRATEGY FOR HIGH-TITER AND HIGH-PURITY PRODUCTION OF 
       MULTI-SUBUNIT PROTEINS SUCH AS ANTIBODIES IN TRANSFORMED MICROBES
        SUCH AS PICHIA PASTORIS

<130>  67858.730202

<140>  tba
<141>  2012-08-20

<150>  61/525,307
<151>  2011-08-19

<150>  13/466,795
<151>  2012-05-08

<160>  54    

<170>  PatentIn version 3.5

<210>  1
<211>  441
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  1

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Leu Asp Leu Ser Ser Tyr 
            20                  25                  30          


Tyr Met Gln Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Gly Val Ile Gly Ile Asn Asp Asn Thr Tyr Tyr Ala Ser Trp Ala Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Thr Thr Val Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Arg Gly Asp Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala 
            100                 105                 110         


Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser 
        115                 120                 125             


Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe 
    130                 135                 140                 


Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly 
145                 150                 155                 160 


Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu 
                165                 170                 175     


Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr 
            180                 185                 190         


Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Ala Arg 
        195                 200                 205             


Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
    210                 215                 220                 


Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
225                 230                 235                 240 


Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                245                 250                 255     


Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
            260                 265                 270         


Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
        275                 280                 285             


Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
    290                 295                 300                 


Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
305                 310                 315                 320 


Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                325                 330                 335     


Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
            340                 345                 350         


Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
        355                 360                 365             


Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
    370                 375                 380                 


Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
385                 390                 395                 400 


Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                405                 410                 415     


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
            420                 425                 430         


Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440     


<210>  2
<211>  111
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  2

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Leu Asp Leu Ser Ser Tyr 
            20                  25                  30          


Tyr Met Gln Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Gly Val Ile Gly Ile Asn Asp Asn Thr Tyr Tyr Ala Ser Trp Ala Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Thr Thr Val Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Arg Gly Asp Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
            100                 105                 110     


<210>  3
<211>  5
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  3

Ser Tyr Tyr Met Gln 
1               5   


<210>  4
<211>  16
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  4

Val Ile Gly Ile Asn Asp Asn Thr Tyr Tyr Ala Ser Trp Ala Lys Gly 
1               5                   10                  15      


<210>  5
<211>  333
<212>  DNA
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  5
gaggtgcagc ttgtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc       60

tcctgtgcag tctctggact cgacctcagt agctactaca tgcaatgggt ccgtcaggct      120

ccagggaagg ggctggagtg ggtcggagtc attggtatca atgataacac atactacgcg      180

agctgggcga aaggccgatt caccatctcc agagacaatt ccaagaccac ggtgtatctt      240

caaatgaaca gcctgagagc tgaggacact gctgtgtatt tctgtgctag aggggacatc      300

tggggccaag ggaccctcgt caccgtctcg agc                                   333


<210>  6
<211>  1326
<212>  DNA
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  6
gaggtgcagc ttgtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc       60

tcctgtgcag tctctggact cgacctcagt agctactaca tgcaatgggt ccgtcaggct      120

ccagggaagg ggctggagtg ggtcggagtc attggtatca atgataacac atactacgcg      180

agctgggcga aaggccgatt caccatctcc agagacaatt ccaagaccac ggtgtatctt      240

caaatgaaca gcctgagagc tgaggacact gctgtgtatt tctgtgctag aggggacatc      300

tggggccaag ggaccctcgt caccgtctcg agcgcctcca ccaagggccc atcggtcttc      360

cccctggcac cctcctccaa gagcacctct gggggcacag cggccctggg ctgcctggtc      420

aaggactact tccccgaacc ggtgacggtg tcgtggaact caggcgccct gaccagcggc      480

gtgcacacct tcccggctgt cctacagtcc tcaggactct actccctcag cagcgtggtg      540

accgtgccct ccagcagctt gggcacccag acctacatct gcaacgtgaa tcacaagccc      600

agcaacacca aggtggacgc gagagttgag cccaaatctt gtgacaaaac tcacacatgc      660

ccaccgtgcc cagcacctga actcctgggg ggaccgtcag tcttcctctt ccccccaaaa      720

cccaaggaca ccctcatgat ctcccggacc cctgaggtca catgcgtggt ggtggacgtg      780

agccacgaag accctgaggt caagttcaac tggtacgtgg acggcgtgga ggtgcataat      840

gccaagacaa agccgcggga ggagcagtac gccagcacgt accgtgtggt cagcgtcctc      900

accgtcctgc accaggactg gctgaatggc aaggagtaca agtgcaaggt ctccaacaaa      960

gccctcccag cccccatcga gaaaaccatc tccaaagcca aagggcagcc ccgagaacca     1020

caggtgtaca ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc     1080

tgcctggtca aaggcttcta tcccagcgac atcgccgtgg agtgggagag caatgggcag     1140

ccggagaaca actacaagac cacgcctccc gtgctggact ccgacggctc cttcttcctc     1200

tacagcaagc tcaccgtgga caagagcagg tggcagcagg ggaacgtctt ctcatgctcc     1260

gtgatgcatg aggctctgca caaccactac acgcagaaga gcctctccct gtctccgggt     1320

aaatga                                                                1326


<210>  7
<211>  219
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  7

Gln Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp 
1               5                   10                  15      


Arg Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Val Tyr Asp Asn Asn 
            20                  25                  30          


Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Gln Leu 
        35                  40                  45              


Ile Tyr Ser Thr Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser 
    50                  55                  60                  


Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln 
65                  70                  75                  80  


Pro Glu Asp Val Ala Thr Tyr Tyr Cys Leu Gly Ser Tyr Asp Cys Ser 
                85                  90                  95      


Ser Gly Asp Cys Phe Val Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110         


Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
        115                 120                 125             


Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 
    130                 135                 140                 


Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
145                 150                 155                 160 


Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
                165                 170                 175     


Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
            180                 185                 190         


Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
        195                 200                 205             


Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215                 


<210>  8
<211>  113
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  8

Gln Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp 
1               5                   10                  15      


Arg Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Val Tyr Asp Asn Asn 
            20                  25                  30          


Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Gln Leu 
        35                  40                  45              


Ile Tyr Ser Thr Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser 
    50                  55                  60                  


Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln 
65                  70                  75                  80  


Pro Glu Asp Val Ala Thr Tyr Tyr Cys Leu Gly Ser Tyr Asp Cys Ser 
                85                  90                  95      


Ser Gly Asp Cys Phe Val Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110         


Arg 
    


<210>  9
<211>  13
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  9

Gln Ala Ser Gln Ser Val Tyr Asp Asn Asn Tyr Leu Ala 
1               5                   10              


<210>  10
<211>  7
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  10

Ser Thr Ser Thr Leu Ala Ser 
1               5           


<210>  11
<211>  13
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  11

Leu Gly Ser Tyr Asp Cys Ser Ser Gly Asp Cys Phe Val 
1               5                   10              


<210>  12
<211>  339
<212>  DNA
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  12
caagtgctga cccagtctcc atcctccctg tctgcatctg taggagacag agtcaccatc       60

aattgccagg ccagtcagag tgtttatgat aacaactacc tagcctggta tcagcagaaa      120

ccagggaaag ttcctaagca actgatctat tctacatcca ctctggcatc tggggtccca      180

tctcgtttca gtggcagtgg atctgggaca gatttcactc tcaccatcag cagcctgcag      240

cctgaagatg ttgcaactta ttactgtcta ggcagttatg attgtagtag tggtgattgt      300

tttgttttcg gcggaggaac caaggtggaa atcaaacgt                             339


<210>  13
<211>  660
<212>  DNA
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  13
caagtgctga cccagtctcc atcctccctg tctgcatctg taggagacag agtcaccatc       60

aattgccagg ccagtcagag tgtttatgat aacaactacc tagcctggta tcagcagaaa      120

ccagggaaag ttcctaagca actgatctat tctacatcca ctctggcatc tggggtccca      180

tctcgtttca gtggcagtgg atctgggaca gatttcactc tcaccatcag cagcctgcag      240

cctgaagatg ttgcaactta ttactgtcta ggcagttatg attgtagtag tggtgattgt      300

tttgttttcg gcggaggaac caaggtggaa atcaaacgta cggtggctgc accatctgtc      360

ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg      420

ctgaataact tctatcccag agaggccaaa gtacagtgga aggtggataa cgccctccaa      480

tcgggtaact cccaggagag tgtcacagag caggacagca aggacagcac ctacagcctc      540

agcagcaccc tgacgctgag caaagcagac tacgagaaac acaaagtcta cgcctgcgaa      600

gtcacccatc agggcctgag ctcgcccgtc acaaagagct tcaacagggg agagtgttag      660


<210>  14
<211>  441
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  14

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Ile Asp Leu Ser Gly Tyr 
            20                  25                  30          


Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Gly Val Ile Gly Ile Asn Gly Ala Thr Tyr Tyr Ala Ser Trp Ala Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Thr Thr Val Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Arg Gly Asp Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala 
            100                 105                 110         


Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser 
        115                 120                 125             


Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe 
    130                 135                 140                 


Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly 
145                 150                 155                 160 


Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu 
                165                 170                 175     


Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr 
            180                 185                 190         


Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Ala Arg 
        195                 200                 205             


Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
    210                 215                 220                 


Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
225                 230                 235                 240 


Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                245                 250                 255     


Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
            260                 265                 270         


Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
        275                 280                 285             


Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
    290                 295                 300                 


Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
305                 310                 315                 320 


Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                325                 330                 335     


Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
            340                 345                 350         


Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
        355                 360                 365             


Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
    370                 375                 380                 


Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
385                 390                 395                 400 


Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                405                 410                 415     


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
            420                 425                 430         


Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440     


<210>  15
<211>  111
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  15

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Ile Asp Leu Ser Gly Tyr 
            20                  25                  30          


Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Gly Val Ile Gly Ile Asn Gly Ala Thr Tyr Tyr Ala Ser Trp Ala Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Thr Thr Val Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Arg Gly Asp Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
            100                 105                 110     


<210>  16
<211>  5
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  16

Gly Tyr Tyr Met Asn 
1               5   


<210>  17
<211>  15
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  17

Ile Gly Ile Asn Gly Ala Thr Tyr Tyr Ala Ser Trp Ala Lys Gly 
1               5                   10                  15  


<210>  18
<211>  333
<212>  DNA
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  18
gaggtgcagc ttgtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc       60

tcctgtgcag tctctggaat cgacctcagt ggctactaca tgaactgggt ccgtcaggct      120

ccagggaagg ggctggagtg ggtcggagtc attggtatta atggtgccac atactacgcg      180

agctgggcga aaggccgatt caccatctcc agagacaatt ccaagaccac ggtgtatctt      240

caaatgaaca gcctgagagc tgaggacact gctgtgtatt tctgtgctag aggggacatc      300

tggggccaag ggaccctcgt caccgtctcg agc                                   333


<210>  19
<211>  1326
<212>  DNA
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  19
gaggtgcagc ttgtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc       60

tcctgtgcag tctctggaat cgacctcagt ggctactaca tgaactgggt ccgtcaggct      120

ccagggaagg ggctggagtg ggtcggagtc attggtatta atggtgccac atactacgcg      180

agctgggcga aaggccgatt caccatctcc agagacaatt ccaagaccac ggtgtatctt      240

caaatgaaca gcctgagagc tgaggacact gctgtgtatt tctgtgctag aggggacatc      300

tggggccaag ggaccctcgt caccgtctcg agcgcctcca ccaagggccc atcggtcttc      360

cccctggcac cctcctccaa gagcacctct gggggcacag cggccctggg ctgcctggtc      420

aaggactact tccccgaacc ggtgacggtg tcgtggaact caggcgccct gaccagcggc      480

gtgcacacct tcccggctgt cctacagtcc tcaggactct actccctcag cagcgtggtg      540

accgtgccct ccagcagctt gggcacccag acctacatct gcaacgtgaa tcacaagccc      600

agcaacacca aggtggacgc gagagttgag cccaaatctt gtgacaaaac tcacacatgc      660

ccaccgtgcc cagcacctga actcctgggg ggaccgtcag tcttcctctt ccccccaaaa      720

cccaaggaca ccctcatgat ctcccggacc cctgaggtca catgcgtggt ggtggacgtg      780

agccacgaag accctgaggt caagttcaac tggtacgtgg acggcgtgga ggtgcataat      840

gccaagacaa agccgcggga ggagcagtac gccagcacgt accgtgtggt cagcgtcctc      900

accgtcctgc accaggactg gctgaatggc aaggagtaca agtgcaaggt ctccaacaaa      960

gccctcccag cccccatcga gaaaaccatc tccaaagcca aagggcagcc ccgagaacca     1020

caggtgtaca ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc     1080

tgcctggtca aaggcttcta tcccagcgac atcgccgtgg agtgggagag caatgggcag     1140

ccggagaaca actacaagac cacgcctccc gtgctggact ccgacggctc cttcttcctc     1200

tacagcaagc tcaccgtgga caagagcagg tggcagcagg ggaacgtctt ctcatgctcc     1260

gtgatgcatg aggctctgca caaccactac acgcagaaga gcctctccct gtctccgggt     1320

aaatga                                                                1326


<210>  20
<211>  219
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  20

Gln Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp 
1               5                   10                  15      


Arg Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Val Tyr His Asn Thr 
            20                  25                  30          


Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Gln Leu 
        35                  40                  45              


Ile Tyr Asp Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser 
    50                  55                  60                  


Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln 
65                  70                  75                  80  


Pro Glu Asp Val Ala Thr Tyr Tyr Cys Leu Gly Ser Tyr Asp Cys Thr 
                85                  90                  95      


Asn Gly Asp Cys Phe Val Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110         


Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
        115                 120                 125             


Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 
    130                 135                 140                 


Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
145                 150                 155                 160 


Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
                165                 170                 175     


Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
            180                 185                 190         


Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
        195                 200                 205             


Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215                 


<210>  21
<211>  113
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  21

Gln Val Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp 
1               5                   10                  15      


Arg Val Thr Ile Asn Cys Gln Ala Ser Gln Ser Val Tyr His Asn Thr 
            20                  25                  30          


Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Gln Leu 
        35                  40                  45              


Ile Tyr Asp Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser 
    50                  55                  60                  


Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln 
65                  70                  75                  80  


Pro Glu Asp Val Ala Thr Tyr Tyr Cys Leu Gly Ser Tyr Asp Cys Thr 
                85                  90                  95      


Asn Gly Asp Cys Phe Val Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110         


Arg 
    


<210>  22
<211>  13
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  22

Gln Ala Ser Gln Ser Val Tyr His Asn Thr Tyr Leu Ala 
1               5                   10              


<210>  23
<211>  7
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  23

Asp Ala Ser Thr Leu Ala Ser 
1               5           


<210>  24
<211>  13
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  24

Leu Gly Ser Tyr Asp Cys Thr Asn Gly Asp Cys Phe Val 
1               5                   10              


<210>  25
<211>  339
<212>  DNA
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  25
caagtgctga cccagtctcc atcctccctg tctgcatctg taggagacag agtcaccatc       60

aattgccagg ccagtcagag tgtttatcat aacacctacc tggcctggta tcagcagaaa      120

ccagggaaag ttcctaagca actgatctat gatgcatcca ctctggcatc tggggtccca      180

tctcgtttca gtggcagtgg atctgggaca gatttcactc tcaccatcag cagcctgcag      240

cctgaagatg ttgcaactta ttactgtctg ggcagttatg attgtactaa tggtgattgt      300

tttgttttcg gcggaggaac caaggtggaa atcaaacgt                             339


<210>  26
<211>  660
<212>  DNA
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  26
caagtgctga cccagtctcc atcctccctg tctgcatctg taggagacag agtcaccatc       60

aattgccagg ccagtcagag tgtttatcat aacacctacc tggcctggta tcagcagaaa      120

ccagggaaag ttcctaagca actgatctat gatgcatcca ctctggcatc tggggtccca      180

tctcgtttca gtggcagtgg atctgggaca gatttcactc tcaccatcag cagcctgcag      240

cctgaagatg ttgcaactta ttactgtctg ggcagttatg attgtactaa tggtgattgt      300

tttgttttcg gcggaggaac caaggtggaa atcaaacgta cggtggctgc accatctgtc      360

ttcatcttcc cgccatctga tgagcagttg aaatctggaa ctgcctctgt tgtgtgcctg      420

ctgaataact tctatcccag agaggccaaa gtacagtgga aggtggataa cgccctccaa      480

tcgggtaact cccaggagag tgtcacagag caggacagca aggacagcac ctacagcctc      540

agcagcaccc tgacgctgag caaagcagac tacgagaaac acaaagtcta cgcctgcgaa      600

gtcacccatc agggcctgag ctcgcccgtc acaaagagct tcaacagggg agagtgttag      660


<210>  27
<211>  1350
<212>  DNA
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  27
gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc       60

tcctgtgcag cctctggatt ctccctcagt aactactacg tgacctgggt ccgtcaggct      120

ccagggaagg ggctggagtg ggtcggcatc atctatggta gtgatgaaac cgcctacgct      180

acctccgcta taggccgatt caccatctcc agagacaatt ccaagaacac cctgtatctt      240

caaatgaaca gcctgagagc tgaggacact gctgtgtatt actgtgctag agatgatagt      300

agtgactggg atgcaaagtt caacttgtgg ggccaaggga ccctcgtcac cgtctcgagc      360

gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg      420

ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg      480

tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca      540

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc      600

tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagag agttgagccc      660

aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga      720

ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct      780

gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg      840

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacgcc      900

agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag      960

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc     1020

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggaggag     1080

atgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc     1140

gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg     1200

ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg     1260

cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg     1320

cagaagagcc tctccctgtc tccgggtaaa                                      1350


<210>  28
<211>  450
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  28

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr 
            20                  25                  30          


Tyr Val Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Gly Ile Ile Tyr Gly Ser Asp Glu Thr Ala Tyr Ala Thr Ser Ala Ile 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      


Arg Asp Asp Ser Ser Asp Trp Asp Ala Lys Phe Asn Leu Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
        115                 120                 125             


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
    130                 135                 140                 


Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
145                 150                 155                 160 


Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175     


Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
            180                 185                 190         


Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
225                 230                 235                 240 


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                245                 250                 255     


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
        275                 280                 285             


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg 
    290                 295                 300                 


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
            340                 345                 350         


Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
385                 390                 395                 400 


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                405                 410                 415     


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Lys 
    450 


<210>  29
<211>  651
<212>  DNA
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  29
gctatccaga tgacccagtc tccttcctcc ctgtctgcat ctgtaggaga cagagtcacc       60

atcacttgcc aggccagtca gagcattaac aatgagttat cctggtatca gcagaaacca      120

gggaaagccc ctaagctcct gatctatagg gcatccactc tggcatctgg ggtcccatca      180

aggttcagcg gcagtggatc tgggacagac ttcactctca ccatcagcag cctgcagcct      240

gatgattttg caacttatta ctgccaacag ggttatagtc tgaggaacat tgataatgct      300

ttcggcggag ggaccaaggt ggaaatcaaa cgtacggtgg ctgcaccatc tgtcttcatc      360

ttcccgccat ctgatgagca gttgaaatct ggaactgcct ctgttgtgtg cctgctgaat      420

aacttctatc ccagagaggc caaagtacag tggaaggtgg ataacgccct ccaatcgggt      480

aactcccagg agagtgtcac agagcaggac agcaaggaca gcacctacag cctcagcagc      540

accctgacgc tgagcaaagc agactacgag aaacacaaag tctacgcctg cgaagtcacc      600

catcagggcc tgagctcgcc cgtcacaaag agcttcaaca ggggagagtg t               651


<210>  30
<211>  217
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized antibody sequence

<400>  30

Ala Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Asn Asn Glu 
            20                  25                  30          


Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              


Tyr Arg Ala Ser Thr Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Leu Arg Asn 
                85                  90                  95      


Ile Asp Asn Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr 
            100                 105                 110         


Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu 
        115                 120                 125             


Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro 
    130                 135                 140                 


Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly 
145                 150                 155                 160 


Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr 
                165                 170                 175     


Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His 
            180                 185                 190         


Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val 
        195                 200                 205             


Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215         


<210>  31
<211>  18
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  31

Met Arg Ser Leu Leu Ile Leu Val Leu Cys Phe Leu Pro Leu Ala Ala 
1               5                   10                  15      


Leu Gly 
        


<210>  32
<211>  16
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  32

Met Arg Leu Leu Leu Leu Leu Leu Leu Leu Pro Leu Ala Ala Leu Gly 
1               5                   10                  15      


<210>  33
<211>  19
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  33

Met Leu Leu Gln Ala Phe Leu Phe Leu Leu Ala Gly Phe Ala Ala Lys 
1               5                   10                  15      


Ile Ser Ala 
            


<210>  34
<211>  35
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  34

Met Arg Phe Pro Ser Ile Phe Thr Ala Val Leu Phe Ala Ala Ser Ser 
1               5                   10                  15      


Ala Leu Ala Ala Pro Val Asn Thr Thr Thr Glu Glu Gly Val Ser Leu 
            20                  25                  30          


Glu Lys Arg 
        35  


<210>  35
<211>  22
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  35

Met Arg Phe Pro Ser Ile Phe Thr Ala Val Leu Phe Ala Ala Ser Ser 
1               5                   10                  15      


Ala Leu Ala Ala Pro Val 
            20          


<210>  36
<211>  27
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  36

Met Arg Phe Pro Ser Ile Phe Thr Ala Val Leu Phe Ala Ala Ser Ser 
1               5                   10                  15      


Ala Leu Ala Ala Pro Val Ser Leu Glu Lys Arg 
            20                  25          


<210>  37
<211>  41
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  37

Met Arg Phe Pro Ser Ile Phe Thr Ala Val Leu Phe Ala Ala Ser Ser 
1               5                   10                  15      


Ala Leu Ala Ala Pro Val Asn Thr Thr Thr Glu Glu Gly Val Ser Leu 
            20                  25                  30          


Glu Lys Arg Glu Ala Glu Ala Glu Ala 
        35                  40      


<210>  38
<211>  85
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  38

Met Arg Phe Pro Ser Ile Phe Thr Ala Val Leu Phe Ala Ala Ser Ser 
1               5                   10                  15      


Ala Leu Ala Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln 
            20                  25                  30          


Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe 
        35                  40                  45              


Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu 
    50                  55                  60                  


Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val 
65                  70                  75                  80  


Ser Leu Glu Lys Arg 
                85  


<210>  39
<211>  44
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  39

Met Thr Lys Pro Thr Gln Val Leu Val Arg Ser Val Ser Ile Leu Phe 
1               5                   10                  15      


Phe Ile Thr Leu Leu His Leu Val Val Ala Leu Asn Asp Val Ala Gly 
            20                  25                  30          


Pro Ala Glu Thr Ala Pro Val Ser Leu Leu Pro Arg 
        35                  40                  


<210>  40
<211>  22
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  40

Met Phe Ser Pro Ile Leu Ser Leu Glu Ile Ile Leu Ala Leu Ala Thr 
1               5                   10                  15      


Leu Gln Ser Val Phe Ala 
            20          


<210>  41
<211>  22
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  41

Met Gln Thr Leu Leu Val Ser Ser Leu Val Val Ser Leu Ala Ala Ala 
1               5                   10                  15      


Leu Pro His Tyr Ile Arg 
            20          


<210>  42
<211>  22
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  42

Met Ile Phe Leu Lys Leu Ile Lys Ser Ile Val Ile Gly Leu Gly Leu 
1               5                   10                  15      


Val Ser Ala Ile Gln Ala 
            20          


<210>  43
<211>  24
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  43

Met Lys Trp Val Thr Phe Ile Ser Leu Leu Phe Leu Phe Ser Ser Ala 
1               5                   10                  15      


Tyr Ser Arg Gly Val Phe Arg Arg 
            20                  


<210>  44
<211>  18
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  44

Met Lys Trp Val Thr Phe Ile Ser Leu Leu Phe Leu Phe Ser Ser Ala 
1               5                   10                  15      


Tyr Ser 
        


<210>  45
<211>  24
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  45

Met Ala Leu Trp Met Arg Leu Leu Pro Leu Leu Ala Leu Leu Ala Leu 
1               5                   10                  15      


Trp Gly Pro Asp Pro Ala Ala Ala 
            20                  


<210>  46
<211>  24
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  46

Met Lys Tyr Thr Ser Tyr Ile Leu Ala Phe Gln Leu Cys Ile Val Leu 
1               5                   10                  15      


Gly Ser Leu Gly Cys Asp Leu Pro 
            20                  


<210>  47
<211>  26
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  47

Met Ala Ala Asp Ser Gln Thr Pro Trp Leu Leu Thr Phe Ser Leu Leu 
1               5                   10                  15      


Cys Leu Leu Trp Pro Gln Glu Pro Gly Ala 
            20                  25      


<210>  48
<211>  27
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  48

Met Lys Lys Asn Arg Met Met Met Met Ile Trp Ser Val Gly Val Val 
1               5                   10                  15      


Trp Met Leu Leu Leu Val Gly Gly Ser Tyr Gly 
            20                  25          


<210>  49
<211>  18
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  49

Met Gln Lys Leu Ile Ile Phe Ala Leu Val Val Leu Cys Val Gly Ser 
1               5                   10                  15      


Glu Ala 
        


<210>  50
<211>  18
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  50

Met Lys Ala Leu Ile Val Leu Gly Leu Val Leu Leu Ser Val Thr Val 
1               5                   10                  15      


Gln Gly 
        


<210>  51
<211>  20
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  51

Met Val Asp Gly Val Met Ile Leu Pro Val Leu Ile Met Ile Ala Leu 
1               5                   10                  15      


Pro Ser Pro Ser 
            20  


<210>  52
<211>  19
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  52

Met Gly Ala Ala Ala Lys Leu Ala Phe Ala Val Phe Leu Ile Ser Cys 
1               5                   10                  15      


Ser Ser Gly 
            


<210>  53
<211>  31
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  53

Met Leu Ser Leu Lys Pro Ser Trp Leu Thr Leu Ala Ala Leu Met Tyr 
1               5                   10                  15      


Ala Met Leu Leu Val Val Val Pro Phe Ala Lys Pro Val Arg Ala 
            20                  25                  30      


<210>  54
<211>  22
<212>  PRT
<213>  Artificial

<220>
<223>  Secretion signal peptide

<400>  54

Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp 
1               5                   10                  15      


Leu Pro Gly Ala Lys Cys 
            20          


